Macr,ophage

Canc er c,eu
Hollpe r T ce,11

• •••
• • ••• •••
• •• •• • •
Natu ral
:Kl'l ler c,eml Cytot oxic T cell
 Th,e 1p r ofessio,nal anhg ,e n-J)res,e nting cens in the
1

finail comn:11on pa'lh1vvay f1 o r a.ctivath1g :n a·fv,e T

c,e,Us .

'~ --
- '· ·' -

r&,• · -~• ...M

A novel subs,al of den<.1r1t1c cells llf f\J-p-rodu.c,ng killer DC) [IKDC)·
TRAtL8 perfonn• tumor cell lys~.s~vaa T ce.lL IFN-~ -ang1ogenes1a
 ' .• ,' I .' '·

-- upregu lat1ng MHC class I. tumor antigens . and

r1dhes 1on n1olecules. promoting ac t1v1ty of B and T cells.
n1acrophagcs and dendrit1c cells
-- T cell growth factor that binds to a specifi c tripartite
recepto r on T cells
- pro moting N K and T cell activ ity . and a growth facto r
for B cells
( G r.1nuIocy!e-n1onocy!t- colony st,ri1Lllct l1nq f a,;tor ) --
recon slltutIng antigen-prese nting c e lls.
 or ,.,.,.___ tion

.
• NA GE i
MA RT I
C'D 'A• )

~
" '••···
lyn ,pt ,, ., .
.
Nl sra'c Jon f'.:.-o
Ip m p h 11ru1 ,de
1
 MECHANJSl\1S OF AVOIDING OF IMMUNOBIOLOGIC...\L
TUMOR CONTROL
o Tumor cells don't express (or in low quantities) MHC I
molecules
o Tumors don't express CD28 and CD86 (coreceptors in T-ce
immune response)
o Tumor can induce antibodies which don't destroy it but
prevent it's destruction
o Membrane tumor AGs can be changed
o Tumor cells can produce soluble forms of AGs which
intercept specific effector cells and antibodies
o Tumor cells genes can mutate
o Tumor cells secrete immunosuppressive cytokines
o Immune tolerance against tumor can be formed
 l\1E CfJ ~\NI SM S C>J~ ,,,..,)ID ING OF 11\11\fl] NO B IOL O GIC AIJ
TU l\101{ CO N'I' l~U L
c Tu mo r ce1ls don 't exp res s (or in l o·w qu ant itie s) MH C I
1

mo lec ule s
o Tu mo rs don.' t ex·p res s CD 28 an d CD 86 (oo rec ept ors in T- ce·
1
1

im mu ne res pon se)

Tu mor c~n in d·u ce e nti bod ies w'h ich d on 't d est roy it bu t
1
1
1 1 1

pre ven t i.t's des tru cti on -

o Me mb ran e tum or AG s can be cha ng ed
o Tu mo r cel ls can pro duc e sol ubl e for ms of·A Gs which
int erc ept specific eff ect or cel ls a ·n d an)tibod.ies
o Tu Jno r cel ls gen es can mu ta.t e,
1

t Tu mo r cel ls. secr-ete im. mu no su:p pre ssi ve cyt oki nes
o Im mu ne tol era nc·e age .in st tum or can be for me d
TlJl\iOR i\NTIGENS
T L1n1r>1~ A [Js s 1~cci fi cit)'
-:• Unique
~ I=:.
~- T· umor-s 11
l
~~c
❖j . e-apecri6
T1ssu. '-~c·

-~ Cao.di.dates
1

Product-a of gene. .suppr,e esor

. Virus associated
ttf'~t;lU JH.J£1Vl l£N 'Jl~;1··u IJJ~AJ_J
ONCOMARIIBR
c OM in 'P rod,uced only maliplall.t tumors
1

o 0 M is o,r ,g,a n. specific:

1

o 0 M is detect;e d in high concentration in bio1]ogic,a l fl'uids

1
1

o OM concentration co rrelates with tumor size

1 1

c OM concent:r atio,n correlates with stage of diseases

1

o OM concentration correlate& with prognosis

o OM conc,e ntra.t ion correlates with treatment effect

1

OM permits to diagnose, the wl1ole tumor

BASIC SYSTEl\;{S OF
1

fMl\10NOLOGICl-\J-' IN'rl~llACrl~IONS

• MOTHER - FATHER

[I 'M OTHER-FETUS
 S~ s ten°t <~111otl1er -fa tl1e1~~,.
1

Local imntani·t y 0 r w·o m,e n. reprodu,c tive organ.a:

1
1

. :. Macrophage;&, ne·u trop,h yls, NK-phagocytos.is of spermatozoids

·=· JgG, lgA --s·p ermatozoid.s agglutination

~,:., pH low· means

C&'UBes of non-reject.i on
1
of aperm,a ta·z ois
1

❖ Women locs.l iimm·u n·i ty is insufficient fo1r neutralization of 1

sper-m a·t ozoids a ction

1

-:■ S,y stemic immun,o logical t'leaction don't ,d e·v~lop due 'to•rela.t iv·e iso'l ati,on
1 1

of wom,e n reprod.uct1ve org·a ns from bloodstream.

❖ Ejaculatie co·n.tains.immunoauppressive substances
 Sys ten i ccn1other-fetus>>
Em bry o anti gen s

❖ 1 gruu p - fath er alloa ntig·c ns

-:~ 2 grou p - emb ryo-.caus.ed; they appe ar in vari able stag,e s of emb ry0
1
1

,d ev,e lopm ent

❖ 3 gro up- macTomolecul ar subs ta,nices in w,o,m en geni tal 'trac t whie'h
1

bec,o me anti,g en prop e,t i es, afte r cont act 'With ejac ulate
1

Cau sels of em.b ryon al AGa non -rej ecti on

+:- Plac enta l ·b arrie r ,(t'pophobl ast)
1
1

-:- Indu ctio n of selecti-ve supp ress io'n of em·b ryo AG,s of mate rnal cells
1

■:- Syn th.e sis of sttb,s tan,ces S't.1,p pres s ing rejie ction by plac enta
1
,THE~LACENtAL 118BBH!B EK ll fiP!A\1111 I CH IA
gYl"CJTl~Ol ~ I lODL A.:.iiT
:;iiVN C ..,,,, I•~
r nt<-tP, ,on1 At.3r
l tLA 0 ---===-----'I CY-I Q f (;;p o 1~ , IUBLf\5 1
Co■np1a1ncud
iEJ:Cli1n tral pr&Tnln!!!!
II 1
==---..R D!:11 ~fc.t 11'11: n
la O'V'IOIDJCk:ll'y'
I X~liilr AE M l.;ll~VIJ N IIC
~ Mf 6(:l t:_<RM

,
, 7
A It., -..::.. ■1 "1 1 1 ff_ l!.:1' l _ n- F Anflgnt'I 1Cl n k aDaoro1nq l
P ltVttll:OU I I IKJI ,1u1 ) Ii/ tlJ h i ~~- i• _•ul MI~I C UI ill U"" <111um u I •
' '•'" t I( ; I • II • ff1 • ·• - I P l ~ l u l C-OII B
~
,I--~ ' . , • • •. • • ~ 11
Laa-al IKll" I R ~ IJ) D
11mrnu1n1:1ntrJPl'f'!ICl !r.!!§ tn n
n &I nllr I 'I.. Uy I 0
PI ..J \C EN TA L I1'U\1U NO I.O GI CA L FU NC TI ON S
Tr,a ns po rt fu nc tio n
c M oth er -> fet us : lgG l-4
o Fe tu s -.> mo the r: alf a-fet~ p~ ote in, est rog en s,
glycocorticos·t ero i ds., WBC s , RBC s
1

Ba rr ier fu nc tio n
o C'o mp.lem en t ina cti v·a tio n an d ,a nti -pa.te,r na l an tib od ies
'

so rpt 1on1

Im mu n,o re gu la tin g fu nc tio n

o Sy ntp .es is i.m mu no su pp res siv e ho,r!]lOnes req uir ed for
ke ep ing of 1mmunological b,a ]an ce 1n sy ste m Hmo th.,e r-
1

fet us·t1
o .A bs en c·e of MH C I mo lec ule s lea ds to ,a nti -em bry o
cy to,t ox ici ty du ,e to ab,s en ce of p,r ese·n tat ion of AG
 ll\1l\!UNOSUP1.1RESSI\'E FA C'l,OR..S IN NOR!\'L-L\L
1

PREl} N1.tlNC\r

• Early pregn1a nc,y _p hase pr,o tein synth,e sis

• S permatozoids contain TLX.-AG, sensitization ·t o which
1 1

is nec-er&Sary stimulus for' s·ystemic immun.osu.p pr,ession

. d. UCt·I.OD
in

• Macrop.h a.g es suppression

1

• Placenta functions (see below)

1
CAUSES OF BHEAI<E OF C\IJvfUNE TOI1ER1\NC,E
T() s 1~ERI\li\.'l"OZOIDS~ BL1\RTOl Y(~TE .\ND l;,E'I~us
1

AGs
♦ Harm.ones disorders (imbala,n ce· 0 f estrogen.&/
1 1

hea,t agene,s )

• Infe ctious disea.:s es activatin.g local and :sy·s temic

1 1

immunity·

... Proinflammatory cytokines production

•· Endocrinic•immune dis.or,d ers (lgG2 can ·be cytopathgenic £or·

tro·phoblas·t)
 (l\11\IUNOLOGI CAL CAUSES OF INFE.RTILJTY
✓Secondary and primary immune deficiency
✓Antigamete immunity (10-15% unclear infertility)

✓Autoimmunity to women sexual cells (carriers of HLA-DR3. B8)

✓Antiphospholipid antibodi.e s

✓ Immu~oaenetic simil,rity (in s,iJpila_rity of maternal and paternal

HLA-p henotype.s re·q_wred sens1t1za't1on of pregnant women_to
1

paternal AGs, ie a.b se·n t and..necessary immunosu.p _p ressio1n isntt

induced)

✓Rhesus-conflict
. . (mother Rh-, fetus Rh+) leads to prepancy
d_ete·r m1nat10n
1